Compounds and methods of modulating angiogenesis

Abstract

A pharmaceutical composition includes a synthetic peptide consisting of about 10 to about 50 amino acids and having an amino acid sequence substantially homologous to consecutive amino acids of a portion of the cytoplasmic domain of at least one of α v β 3 integrin or VEGFR2 that includes a tyrosine residue, the amino acid sequence of the peptide including a phosphorylated tyrosine residue or a γ-carboxyglutamic acid residue that is substituted for a corresponding tyrosine residue of the portion of the cytoplasmic domain of α v β 3 integrin or VEGFR2.

Having described the invention, the following is claimed: 
     
       1. A pharmaceutical composition comprising: a synthetic peptide, the peptide comprises an amino acid sequence substantially homologous to about 5 to about 30 consecutive amino acids of a portion of the cytoplasmic domain of α v β 3  integrin that includes a tyrosine residue, the amino acid sequence is selected from the group consisting of: SEQ ID NO: 4, SEQ ID NO: 7, and SEQ ID NO: 8, the peptide is about 10 to about 50 amino acids in length, and the peptide inhibits interaction of α v β 3  integrin with VEGFR2. 
     
     
       2. The pharmaceutical composition of  claim 1 , the peptide not inhibiting natural ligand binding to the α v β 3  integrin. 
     
     
       3. The pharmaceutical composition of  claim 1 , the peptide inhibiting tyrosine phosphorylation of the α v β 3  integrin. 
     
     
       4. The pharmaceutical composition of  claim 1 , the peptide inhibiting tyrosine phosphorylation of VEGFR2 upon VEGF stimulation. 
     
     
       5. The pharmaceutical composition of  claim 1 , the peptide competing with α v β 3  integrin for interaction with VEGFR2. 
     
     
       6. The pharmaceutical composition of  claim 1 , the synthetic peptide further comprises a transport moiety that facilitates transport of the synthetic peptide into a cell. 
     
     
       7. A pharmaceutical composition comprising: a synthetic peptide, the peptide comprises an amino acid sequence substantially homologous to about 5 to about 30 consecutive amino acids of a portion of the cytoplasmic domain of α v β 3  integrin that includes a tyrosine residue, the amino acid sequence of the peptide including a γ-carboxyglutamic acid residue that substitutes a corresponding tyrosine residue of the portion of the cytoplasmic domain of α v β 3  integrin, the amino acid sequence is selected from the group consisting of: SEQ ID NO: 4, SEQ ID NO: 7, and SEQ ID NO: 8, the peptide is about 10 to about 50 amino acids in length, and the peptide inhibits interaction of α v β 3  integrin with VEGFR2. 
     
     
       8. The pharmaceutical composition of  claim 7 , the peptide not inhibiting natural ligand binding to the α v β 3  integrin. 
     
     
       9. The pharmaceutical composition of  claim 7 , the peptide inhibiting tyrosine phosphorylation of the α v β 3  integrin. 
     
     
       10. The pharmaceutical composition of  claim 7 , the peptide inhibiting tyrosine phosphorylation of VEGFR2 upon VEGF stimulation. 
     
     
       11. The pharmaceutical composition of  claim 7 , the peptide competing with α v β 3  integrin for interaction with VEGFR2. 
     
     
       12. The pharmaceutical composition of  claim 7 , the synthetic peptide further comprises a transport moiety that facilitates transport of the synthetic peptide into a cell.